Glucocorticoid (GC)-induced leucine zipper (GILZ) has been shown to mediate or mimic several actions of GC. This study assessed the role of GILZ in self-resolving and GC-induced resolution of neutrophilic inflammation induced by LPS in mice. GILZ expression was increased during the resolution phase of LPS-induced pleurisy, especially in macrophages with resolving phenotypes. Pretreating LPS-injected mice with trans-activator of transcription peptide (TAT)–GILZ, a cell-permeable GILZ fusion protein, shortened resolution intervals and improved resolution indices. Therapeutic administration of TAT-GILZ induced inflammation resolution, decreased cytokine levels, and promoted caspase-dependent neutrophil apoptosis. TAT-GILZ also modulated the activation of the survival-controlling proteins ERK1/2, NF-κB and Mcl-1. GILZ deficiency was associated with an early increase of annexin A1 (AnxA1) and did not modify the course of neutrophil influx induced by LPS. Dexamethasone treatment resolved inflammation and induced GILZ expression that was dependent on AnxA1. Dexamethasone-induced resolution was not altered in GILZ^−/− mice due to compensatory expression and action of AnxA1. Our results show that therapeutic administration of GILZ efficiently induces a proapoptotic program that promotes resolution of neutrophilic inflammation induced by LPS. Alternatively, a lack of endogenous GILZ during the resolution of inflammation is compensated by AnxA1 overexpression.

This study tested the hypothesis that the low-grade inflammation presented in patients with bipolar disorder (BD) is associated with expansion of activated T cells, and this activated state may be due to a lack of peripheral regulatory cells. Specifically, we investigated the distribution of monocytes and lymphocyte subsets, and investigated Th1/Th2/Th17 cytokines in plasma by flow cytometry. Twenty-one BD type I patients and 21 age- and sex-matched controls were recruited for this study. BD patients had increased proportions of monocytes (CD14+). Regarding lymphocyte populations, BD patients presented reduced proportions of T cells (CD3+) and cytotoxic T cells (CD3+CD8+). BD patients also exhibited a higher percentage of activated T CD4+CD25+ cells, and a lower percentage of IL-10 expressing Treg cells. Our data shed some light into the underlying mechanisms involved with the chronic low-grade inflammatory profile described in BD patients.

Background: Excessive stress and anxiety can impair learning. The objective structured clinical examination (OSCE) is a valuable tool to assess and promote the acquisition of clinical skills. However, significant OSCE-related stress and anxiety are frequently reported. The aim of this study was to investigate the relationships between physiological stress, self-reported levels of anxiety due to an OSCE, self-efficacy, and the meanings that physical therapy students attribute to their experience with the exam. Design: Concurrent mixed methods study. Methods: A total of 32 students took part in this study. All were enrolled in the third semester of a 10-semester Physical Therapy Bachelor Program. Salivary cortisol levels, self-reported anxiety (State-Trait Anxiety Inventory, STAI) were measured before the OSCE. Exam scores and self-efficacy ratings were also recorded. Correlations between variables were tested with the Pearson correlation, with ɑ at 0.05. Semi-structured interviews were used to explore the personal perspectives of students. Thematic analysis was used to investigate emergent themes. Results: Trait anxiety scores were significantly higher than normative values (p < 0.001). A high proportion of students showed high (STAI> 49) state anxiety (37.5%) and trait anxiety (65.6%). Salivary cortisol was not associated anxiety (p > 0.05). Neither stress nor anxiety correlated with OSCE scores. A moderate and significant direct correlation was found for self-efficacy scores and OSCE scores (r = 0.475, p = 0.007). Students reported that confidence had a calming effect and led to better self-perceived performance. They also reported that the OSCE can provide meaningful learning experiences despite being stressful. Conclusions: A high proportion of our students reported a stable/lingering negative affect. However, neither stress nor anxiety related to OSCE scores. Students’ confidence in their capabilities was correlated with their performance. Their subjective reports suggest that self-confidence may have protected them from the negative effects of stress and anxiety on academic performance.

Markers of low-grade peripheral inflammation have been reported amongst people with epilepsy. The mechanisms underlying this phenomenon are unknown. We attempted to characterize peripheral immune cells and their activation status in people with temporal lobe epilepsy (TLE) and healthy controls. Twenty people with TLE and 19 controls were recruited, and peripheral blood lymphocyte and monocyte subsets evaluated ex vivo by multi-color flow cytometry. People with TLE had higher expression of HLA-DR, CD69, CTLA-4, CD25, IL-23R, IFN-γ, TNF and IL-17 in CD4(+) lymphocytes than controls. Granzyme A, CTLA-4, IL-23R and IL-17 expression was also elevated in CD8(+) T cells from people with TLE. Frequency of HLA-DR in CD19(+) B cells and regulatory T cells CD4(+)CD25(+)Foxp3(+) producing IL-10 was higher in TLE when compared with controls. A negative correlation between CD4(+) expressing co-stimulatory molecules (CD69, CD25 and CTLA-4) with age at onset of seizures was found. The frequency of CD4(+)CD25(+)Foxp3(+) cells was also positively correlated with age at onset of seizures. Immune cells of people with TLE show an activation profile, mainly in effector T cells, in line with the low-grade peripheral inflammation.